Synthesis of potential metabolites of a barbiturate containing two branched side chains
Talab, A.; Cavé, C.; Ménager, S.; Miocque, M.; Lafont, O.
Annales Pharmaceutiques Francaises 47(5): 304-313
1989
ISSN/ISBN: 0003-4509 PMID: 2637650 Document Number: 333955
The two branched side chains of 5-(3-methylbutyl)-5-(2-methylpropyl)-barbituric acid present a tertiary carbon atom, which can be oxidized in vivo by hepatic enzymes. Potential metabolites of this compound are synthesised: the gamma-hydroxy metabolite can be oxidized directly by CrO3 while the beta-hydroxy metabolite can only be prepared by hydration of a double bond. This beta-hydroxybarbiturate then undergoes an alcoholysis leading to an allophanyl-gamma-lactone, which is hydrolysed into a carboxylic lactone, which can give a lactone by decarboxylation. On the other hand, a beta-gamma-dihydroxymetabolite is synthesised by double hydration of two double bonds using two different methods. A spirobilactone can also be synthesised from this dihydroxy compound.